The primary goal of this proposal is an investigation of the effects of the development of barbiturate tolerance on the reinforcing property of CNS depressants. The method for this study will be 1) observations in rhesus monkeys of tolerance development, as measured by shifts in the effects of various doses of pentobarbital on rates of food-reinforced behavior and 2) observation of the effect of this tolerance, in the same animals, on rates and patterns and amounts of intravenous methohexital self-administration. Secondary goals involve investigation of rate and amount of tolerance development to barbiturates and benzodiazepenes as determined by the pharmacological parameters of frequency, amount and duration of drug administration, and by the behavioral parameters of rate of behavior, and density of reinforcement. The method for these studies will be observation of drug effects in pigeons responding at various rates on schedules of food-reinforced operant behavior, and observation in mice on the effects of drugs on locomotor activity.